Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597422
Title: Interactions of Salmonella with the immune system
Author: Chan, S. S. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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Abstract:
Live attenuated Salmonella that express heterologous antigens are attractive vehicles for the presentation of antigens for systemic and mucosal immunity. It is hypothesised that this requires uptake and interaction with DCs although this has yet to be studied in large animal models. This study has used pseudoafferent cannulated sheep to provide physiologically relevant DCs. However, in many other systems in vitro derived DCs are used in studies with Salmonella. Therefore we have cloned and expressed ovine IL-4 and developed protocols for derivation of in vitro generated DCs from comparison with this data. Cannulation of pseudoafferent and efferent lymphatics further allows monitoring of the earliest events of an in vivo Salmonella infection. Following in vitro infection with S. abortus ovis (a sheep specific Salmonella serotype) very few DCs were found to contain intracellular Salmonella. Avirulent Salmonella mutants were rapidly cleared from afferent lymph DCs in vitro unlike their virulent parental strains, which were found to survive and replicate intracellularly. Despite the rapid clearance of attenuated S. abortus ovis mutants from DCs, Maedi Visna virus (MVV) gag antigens expressed in these Salmonella were found to be presented to T cells. Following subcutaneous injection of aroA- S. abortus ovis expressing MVV gag p25, Salmonella were found in the afferent lymph and cells draining the infection site. However, no bacteria were detected in the efferent lymph or cells. Phenotypic changes indicative of enhanced DC maturation in afferent lymph as well as lymphocyte activation in afferent and efferent lymph were also observed. Functional anti-Salmonella immune responses in efferent lymph were also studied. This study has established that Salmonella can infect afferent lymph dendritic cells of a large animal model. Such cells migrate to the lymph node where they initiate immune responses and can influence the cells' activation and the immune mechanisms invoked.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.597422  DOI: Not available
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